Structure and assembly of calcium homeostasis modulator proteins

Syrjanen, Johanna, Michalski, Kevin, Chou, Tsung-Han, Grant, Timothy, Rao, Shanlin, Simorowski, Noriko, Tucker, Stephen, Grigorieff, Nikolaus, Furukawa, Hiro (2019) Structure and assembly of calcium homeostasis modulator proteins. Nature Structural and Molecular Biology. (Submitted)

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Abstract

Biological membranes of many tissues and organs contain large-pore channels designed to permeate a wide variety of ions and metabolites. Examples include connexin, innexin, and pannexin, which form gap junctions and/or bona fide cell surface channels. The most recently identified large-pore channels are the calcium homeostasis modulators (CALHMs), which permeate ions and ATP in a voltage-dependent manner to control neuronal excitability, taste signaling, and pathologies of depression and Alzheimer’s disease. Despite such critical biological roles, the structures and patterns of oligomeric assembly remain unclear. Here, we reveal the first structures of two CALHMs, CALHM1 and CALHM2, by single particle cryo-electron microscopy, which show novel assembly of the four transmembrane helices into channels of 8-mers and 11-mers, respectively. Furthermore, molecular dynamics simulations suggest that lipids can favorably assemble into a bilayer within the larger CALHM2 pore, but not within CALHM1, demonstrating the potential correlation between pore-size, lipid accommodation, and channel activity.

Item Type:	Paper
Subjects:	organs, tissues, organelles, cell types and functions > tissues types and functions > transport > membrane transport
CSHL Authors:	Syrjanen, Johanna L. Michalski, Kevin Simorowski, Noriko Furukawa, Hiro Chou, Tsung-Han
Communities:	CSHL labs > Furukawa lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	2019
Date Deposited:	13 Oct 2023 13:26
Last Modified:	21 Dec 2023 14:35
PMCID:	PMC7015811
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41216

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